DEVELOPMENT OF A SYNTHESIS OF LANKACIDINS - SYNTHESIS OF THE C(14)-C(6) FRAGMENT AND INTRODUCTION OF THE C(10)-C(13) DIENE

Acylation of the azetidinone 8 using the thioester 17, prepared from d imethyl (S)-malate, gave the (3S,4R)-3-(3,4'-bis-tert-butyld imethylsi lyloxy-1'-oxobutyl)azetidinone 18 which was converted into the N-acyl azetidinone 20. Desilylation of this was selective for the primary ter t-butyldimethylsilyl groups and gave mixtures of products in which the 7-membered lactone 25 was the major component rather than the 6-membe red ring isomer required for a lankacidin synthesis. However. the hyls ilyloxy-2'-methyl-1'-oxohex-5-enyl)azetidinone 27 was similarly prepar ed and hydroxyl-induced azetidinone cleavage of the desilylated N-acyl derivative 30 gave the delta-lactone 31. This lactone gave a complex mixture of products on attempted reduction of the ketone substituent, but the required hydroxy lactone 32 could be obtained directly from th e azetidinone 30 using sodium borohydride in ethanol. Introduction of the C(10)-C(13) dienyl fragment into intermediates containing the delt a-lactone was complicated by elimination. However, this diene could be introduced into azetidinone precursors of the delta-lactone using ket o-phosphonate aldehyde condensations.